Note: This document contains side effect information about gemcitabine. Some dosage forms listed on this page may not apply to the brand name Infugem.

Applies to gemcitabine: intravenous powder for solution, intravenous solution.

Serious side effects of Infugem

Along with its needed effects, gemcitabine (the active ingredient contained in Infugem) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking gemcitabine:

More common

• Black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• cloudy urine
• confusion
• cough
• coughing up blood
• diarrhea
• difficult or labored breathing
• difficulty in moving
• difficulty in swallowing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fever
• general feeling of discomfort or illness
• headache
• hoarseness
• increased menstrual flow or vaginal bleeding
• joint pain
• lack or loss of strength
• loss of appetite
• lower back or side pain
• muscle ache, cramps, pain, or stiffness
• nausea
• nosebleeds
• painful or difficult urination
• pale skin
• paralysis
• pinpoint red spots on the skin
• prolonged bleeding from cuts
• rapid weight gain
• red or black, tarry stools
• red or dark brown urine
• runny nose
• shivering
• sores, ulcers, or white spots on the lips or in the mouth
• sore throat
• sweating
• swelling of the hands, ankles, feet, or lower legs
• swelling or inflammation of the mouth
• swollen glands
• swollen joints
• tightness in the chest
• trouble sleeping
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting

Less common

• Chest discomfort
• fast, slow, or irregular heartbeat
• headache (sudden and severe)
• hives, itching, skin rash
• inability to speak
• nervousness
• noisy breathing
• pain or discomfort in the arms, jaw, back, or neck
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seizures
• slurred speech
• temporary blindness
• weakness in the arm or leg or on one side of the body (sudden and severe)

Rare

• Rapid, shallow breathing

Incidence not known

• Blue lips and fingernails
• cloudy urine
• coughing that sometimes produces a pink frothy sputum
• dark urine
• decrease or increase in the amount of urine
• decreased urine output
• difficult, fast, noisy breathing
• dilated neck veins
• extreme tiredness or weakness
• fast, slow, or irregular heartbeat
• general feeling of tiredness or weakness
• increased sweating
• irregular breathing
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• light-colored stools
• sores on the skin, especially on the thighs, breasts, penis, or buttocks
• sores, welts, or blisters
• stomach pain, continuing
• sudden weakness in the arms or legs
• sudden, severe chest pain
• swelling of the face, fingers, feet, or lower legs
• yellow eyes or skin

Other side effects of Infugem

Some side effects of gemcitabine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Difficulty having a bowel movement
• hair loss
• sleepiness or unusual drowsiness
• thinning of hair

Less common

• Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

For Healthcare Professionals

Applies to gemcitabine: intravenous powder for injection, intravenous solution.

Hematologic

Very common (10% or more): Anemia (68%), neutropenia (63%), leucopenia (62%), thrombocytopenia (24%), petechiae (16%), hemorrhage (17%), bone marrow suppression (usually mild to moderate)

Common (1% to 10%): Febrile neutropenia

Very rare (less than 0.01%): Thrombocytosis

Postmarketing reports: Capillary leak syndrome (CLS)^[Ref]

Myelosuppression is the major dose-limiting factor associated with gemcitabine therapy.

Dosage adjustments for hematologic toxicity are frequently necessary. Less than 1% of patients have had to discontinue therapy for either anemia, leukopenia, or thrombocytopenia. Grade 3/4 thrombocytopenia was more common in the elderly, especially older women.

The risk for thrombotic thrombocytopenic purpura increases as the cumulative dose of gemcitabine approaches 20,000 mg/m2.^[Ref]

Gastrointestinal

Very common (10% or more): Nausea/vomiting (69%), diarrhea (19%), stomatitis (11%), stomatitis and ulceration of the mouth (11%)

Common (1% to 10%): Constipation

Very rare (less than 0.01%): Ischemic colitis, anal pruritus^[Ref]

If the patient is not vomiting due to their disease state, nausea can generally be prevented by administration of prochlorperazine or low-dose oral serotonin antagonists and glucocorticoid therapy. One study of 790 patients found the rate of WHO grade 3 nausea and vomiting at a frequency of 22% in patients under 65 years of age, and 12% in patients 65 years of age or older.^[Ref]

Hepatic

No evidence of increased hepatic toxicity has been reported with longer duration or greater total cumulative dose.

Very common (10% or more): Increased ALT (68%), increased AST (67%), increased alkaline phosphatase (55%), hyperbilirubinemia (13%)

Common (1% to 10%):

Uncommon (0.1% to 1%): Serious hepatotoxicity (including liver failure and death), increased gamma-glutamyl transferase (GGT)

Postmarketing reports: Hepatic veno-occlusive disease

Renal

Renal failure may not be reversible, even upon discontinuation of therapy.^[Ref]

Very common (10% or more): Proteinuria (45%), hematuria (35%), increased BUN (16%)

Common (1% to 10%): Increased creatinine (8%)

Uncommon (0.1% to 1%): Renal failure, hemolytic-uremic syndrome^[Ref]

Other

The flu-like symptoms usually take place a few hours after drug administration. The symptoms are usually self-limiting and recovery is generally within 24 to 48 hours. Less than 1% of patients discontinued use due to flu-like symptoms. Some patients get relief from nonsteroidal anti-inflammatory drugs or acetaminophen.

Out of the five reported cases of distal ischemic changes, four of those case related to combination chemotherapy with cisplatin and gemcitabine (the active ingredient contained in Infugem) while one case was of gemcitabine as a single agent in first-line therapy.^[Ref]

Very common (10% or more): Fever (41%), asthenia, chills

Common (1% to 10%): Paresthesia

Rare (less than 0.1%): Radiation toxicity, radiation recall

Frequency not reported: Cough, chills, pattern of tissue injury typically associated with radiation toxicity^[Ref]

Dermatologic

Rash was generally a macular or finely granular maculopapular pruritic eruption, mild to moderate in severity, involving the trunk and extremities. Alopecia is usually minimal.^[Ref]

Very common (10% or more): Allergic skin rash frequently associated with pruritus (30%), alopecia (15%)

Common (1% to 10%): Itching, sweating

Rare (0.01% to 0.1%): Severe skin reactions (including desquamation and bullous skin eruptions), ulceration, vesicle and sore formation, scaling

Very rare (less than 0.01%): Lyell's syndrome (toxic epidermal necrolysis, Stevens Johnson Syndrome

Postmarketing reports: Cellulitis^[Ref]

Respiratory

Some of the dyspnea reported may have been due to underlying disease. Forty percent of the study population consisted of lung cancer patients, while some of the other study patients had pulmonary manifestations of other malignancies.

Different patterns of lung injury may be related to gemcitabine (the active ingredient contained in Infugem) A rapid response following the administration of corticosteroids would mean the respiratory problem was probably due to a hypersensitivity reaction.^[Ref]

Very common (10% or more): Dyspnea (23%)

Common (1% to 10%): Cough, rhinitis

Uncommon (0.1% to 1%): Interstitial pneumonitis, bronchospasm

Rare (0.01% to 0.1%): Pulmonary edema, adult respiratory distress syndrome (ARDS)

Very rare (less than 0.01%): Respiratory failure/death

Frequency not reported: Pulmonary fibrosis, pulmonary edema^[Ref]

Nervous system

Less than 1% of the paresthesias have been severe.^[Ref]

Common (1% to 10%): Headache, insomnia, somnolence, paraesthesia

Uncommon (0.1% to 1%): Cerebrovascular accident

Postmarketing reports: Posterior reversible encephalopathy syndrome (PRES)^[Ref]

Local

Very common (10% or more): Injection site reactions (mainly mild)^[Ref]

Hypersensitivity

Rare (less than 0.1%): Hypersensibility^[Ref]

Cardiovascular

Many of the patients that suffered cardiovascular effects had a prior history of cardiovascular disease. Two percent of patients discontinued therapy due to these effects. Less than 1% of patients discontinued due to edema.^[Ref]

Uncommon (0.1% to 1%): Arrhythmias (predominantly supraventricular), heart failure

Rare (less than 0.1%): Hypotension, hypertension, myocardial infarction, atrial fibrillation

Very rare (less than 0.01%): Congestive heart failure

Postmarketing reports: Supraventricular arrhythmias^[Ref]

Immunologic

Very common (10% or more): Infection (16%), influenza-like symptoms

Rare (less than 0.1%): Anaphylactoid reaction

Frequency not reported: Scleroderma-like reaction^[Ref]

Metabolic

Very common (10% or more): Edema/peripheral edema-including facial edema (usually reversible after stopping treatment)

Common (1% to 10%): Anorexia^[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, myalgia^[Ref]